Greenwood Genetic Center, 106 Gregor Mendel Circle, Greenwood, SC, 29649, USA.
Spectrum Health, Grand Rapids, MI, USA.
Eur J Hum Genet. 2018 Mar;26(3):420-427. doi: 10.1038/s41431-017-0025-y. Epub 2018 Jan 22.
Neural tube defects (NTDs) remain one of the most serious birth defects, and although genes in several pathways have been implicated as risk factors for neural tube defects via knockout mouse models, very few molecular causes in humans have been identified. Whole exome sequencing identified deleterious variants in key apoptotic genes in two families with recurrent neural tube defects. Functional studies in fibroblasts indicate that these variants are loss-of-function, as apoptosis is significantly reduced. This is the first report of variants in apoptotic genes contributing to neural tube defect risk in humans.
神经管缺陷（NTDs）仍然是最严重的出生缺陷之一，尽管通过敲除小鼠模型，已有几个途径的基因被认为是神经管缺陷的风险因素，但在人类中仅鉴定出极少数分子病因。全外显子组测序鉴定出两个复发性神经管缺陷家系中关键凋亡基因的有害变异。成纤维细胞中的功能研究表明，这些变异是功能丧失的，因为细胞凋亡明显减少。这是第一个报道凋亡基因变异导致人类神经管缺陷风险的报告。
